The long range objective is to produce a genetically determined model of essential hypertension in the dog for use in drug testing and investigation of the underlying genetic, biochemical, and physiological mechanisms of this disorder. The specific aim is to establish a line of hypertensive dogs and characterize the pathophysiologic features of hypertension, comparing this line to comparable controls. A colony of hypertensive dogs exists in our laboratory as a result of breeding two unrelated dogs with severe essential hypertension. A breeding plan is proposed to use F1 backcross matings and then select the dogs with the most consistent arterial hypertension to concentrate the genome in four generations. The criteria for selection include direct blood pressure measurements, opthalmologic examination, response to oral sodium load, and response to a pressor agent. The natural history of the disease will be characterized in the breeding dogs over a period of years. Further characterization of hypertension will be done in collaboration with colleagues at a pharmaceutical firm. After a genetic model has been proven and shown to be useful, collaboration with a commercial breeder is proposed to make hypertensive dogs generally available.